APS8, a Polymeric Alkylpyridinium Salt Blocks α7 nAChR and Induces Apoptosis in Non-Small Cell Lung Carcinoma

Marine Drugs

Ana Zovko¹  Kristina Viktorsson⁵  Rolf Lewensohn⁵  Katja Koloᘚ³  Metka Filipič³  Hong Xing²  William R. Kem²  Laura Paleari⁴ 

[1] Department of Biology, Biotechnical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia; E-Mail:;Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, FL 32610, USA; E-Mails:;Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, 1000 Ljubljana, Slovenia; E-Mails:;Epidemiology, Biostatistics and Clinical Trials, IRCCS A.O.U. S. Martino-IST, National Institute for Cancer Research, 16132 Genoa, Italy; E-Mail:;Department of Oncology and Pathology, Karolinska Biomics Center, Karolinska Institutet, 17176 Stockholm, Sweden; E-Mails:

关键词: 3-alkylpyridinium polymers;    apoptosis;    nicotine;    nicotinic acetylcholine receptor;    non-small cell lung carcinoma;   

DOI  :  10.3390/md11072574

来源: mdpi

【 摘 要 】

Naturally occurring 3-alkylpyridinium polymers (poly-APS) from the marine sponge Reniera sarai, consisting of monomers containing polar pyridinium and nonpolar alkyl chain moieties, have been demonstrated to exert a wide range of biological activities, including a selective cytotoxicity against non-small cell lung cancer (NSCLC) cells. APS8, an analog of poly-APS with defined alkyl chain length and molecular size, non-competitively inhibits α7 nicotinic acetylcholine receptors (nAChRs) at nanomolar concentrations that are too low to be acetylcholinesterase (AChE) inhibitory or generally cytotoxic. In the present study we show that APS8 inhibits NSCLC tumor cell growth and activates apoptotic pathways. APS8 was not toxic for normal lung fibroblasts. Furthermore, in NSCLC cells, APS8 reduced the adverse anti-apoptotic, proliferative effects of nicotine. Our results suggest that APS8 or similar compounds might be considered as lead compounds to develop antitumor therapeutic agents for at least certain types of lung cancer.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.